Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD

NCT ID: NCT01709695

Last Updated: 2018-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2013-12-31

Brief Summary

This study proposes to evaluate the effects of guanfacine extended release on brain activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD subjects randomized to placebo treatment.

This study also proposes to collect DNA on study participants, to examine the genetic underpinning of the observed fMRI activation profiles at baseline and in response to treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other related targets) for genetic biomarkers in association with the fMRI findings of this study.

Detailed Description

This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in 12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM) (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo treatment. Children will be comprehensively assessed using a variety of clinical and neuropsychological measures. They will be scanned at baseline while performing both the go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002, 2003)) and the Stay Alert task - a new task designed to measure the arousal component of attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in accordance with titration and dosing strategies used in recent Phase III dose optimization trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI scans will be conducted using a dedicated research 3.0 T Siemens scanner.

Conditions

ADHD; Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

guanfacine hydrochloride XR

Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily

Group Type: EXPERIMENTAL

Guanfacine Hydrochloride XR

Intervention Type: DRUG

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Placebo Group

Flexible dose titration of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Interventions

Guanfacine Hydrochloride XR

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Intervention Type: DRUG

Placebo

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Intervention Type: DRUG

Other Intervention Names

INTUNIV non-stimulant medication; GXR

Eligibility Criteria

Inclusion Criteria

• Diagnosis of any subtype of ADHD
• Normal findings on physical exam, laboratory studies, vital signs, and ECG
• Weight = 60 kgs or less
• Able to complete study procedures and swallow capsules;
• Willing to commit to the entire visit schedule
• Off treatment or have been discontinued from their previous medication for two weeks.

Exclusion Criteria

• Psychiatric comorbidity except Oppositional Defiant Disorder [ODD], Simple Phobia, and dysthymia (unless ongoing medication treatment is required);
• Currently a suicide risk, has previously made a suicide attempt or has a prior history of suicidal behavior;
• Has failed treatment with an adequate trial of an alpha-2 adrenergic agonist;
• Known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride.

Children may not:

• be treated with systemic medication for a medical or psychiatric illness that have CNS effects or affect cognitive function;
• have a known history or presence of structural cardiac abnormalities, exercise-related cardiac events, or clinically significant bradycardia;
• have orthostatic hypotension or a known history of hypertension;
• have an abnormal ECG that is deemed clinically significant;
• have a history of alcohol or other substance abuse or dependence within the last 6 months;
• use any medications that affect BP or heart rate (excluding the subject's current ADHD medication at screening);
• use another investigational medicinal product or participation in a clinical study within 30 days prior to the baseline visit;
• be significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts;
• have body weight of less than 25kg;
• have a clinically important abnormality on urine drug and alcohol screen (excluding the subject's current ADHD stimulant, if applicable);
• be female and currently pregnant or lactating;
• have symptoms indicative of a primary sleep disorder.
• have braces or other metal permanently placed within their body.
• be too anxious to tolerate the fMRI procedure, or be claustrophobic.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Newcorn

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Newcorn, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.

Reference Type: RESULT

PMID: 25659477 (View on PubMed)

Other Identifiers

HSM:10-00415

Identifier Type: -

Identifier Source: secondary_id

GCO 09-1825

Identifier Type: -

Identifier Source: org_study_id